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Hypoxia augments outgrowth endothelial cell (OEC) sprouting and directed migration in response to sphingosine-1-phosphate (S1P)
- Source :
- PLoS ONE, Vol 10, Iss 4, p e0123437 (2015), PLoS ONE, PloS one, vol 10, iss 4
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- Therapeutic angiogenesis provides a promising approach to treat ischemic cardiovascular diseases through the delivery of proangiogenic cells and/or molecules. Outgrowth endothelial cells (OECs) are vascular progenitor cells that are especially suited for therapeutic strategies given their ease of noninvasive isolation from umbilical cord or adult peripheral blood and their potent ability to enhance tissue neovascularization. These cells are recruited to sites of vascular injury or tissue ischemia and directly incorporate within native vascular endothelium to participate in neovessel formation. A better understanding of how OEC activity may be boosted under hypoxia with external stimulation by proangiogenic molecules remains a challenge to improving their therapeutic potential. While vascular endothelial growth factor (VEGF) is widely established as a critical factor for initiating angiogenesis, sphingosine-1-phosphate (S1P), a bioactive lysophospholipid, has recently gained great enthusiasm as a potential mediator in neovascularization strategies. This study tests the hypothesis that hypoxia and the presence of VEGF impact the angiogenic response of OECs to S1P stimulation in vitro. We found that hypoxia altered the dynamically regulated S1P receptor 1 (S1PR1) expression on OECs in the presence of S1P (1.0 μM) and/or VEGF (1.3 nM). The combined stimuli of S1P and VEGF together promoted OEC angiogenic activity as assessed by proliferation, wound healing, 3D sprouting, and directed migration under both normoxia and hypoxia. Hypoxia substantially augmented the response to S1P alone, resulting in ~6.5-fold and ~25-fold increases in sprouting and directed migration, respectively. Overall, this report highlights the importance of establishing hypoxic conditions in vitro when studying ischemia-related angiogenic strategies employing vascular progenitor cells.
- Subjects :
- Vascular Endothelial Growth Factor A
Angiogenesis
Gene Expression
lcsh:Medicine
Regenerative Medicine
Cardiovascular
Neovascularization
chemistry.chemical_compound
Glucuronic Acid
Cell Movement
Sphingosine
Receptors
lcsh:Science
S1PR1
Multidisciplinary
Hexuronic Acids
Stem Cells
Hydrogels
Cell Hypoxia
Vascular endothelial growth factor
Endothelial stem cell
Receptors, Lysosphingolipid
medicine.anatomical_structure
Stem Cell Research - Nonembryonic - Non-Human
Biological Assay
medicine.symptom
Research Article
Endothelium
General Science & Technology
Alginates
Neovascularization, Physiologic
Biology
Vascular
medicine
Human Umbilical Vein Endothelial Cells
Humans
Therapeutic angiogenesis
Physiologic
Sphingosine-1-Phosphate Receptors
Cell Proliferation
Wound Healing
lcsh:R
Stem Cell Research
Oxygen
chemistry
Lysosphingolipid
Immunology
Cancer research
lcsh:Q
Endothelium, Vascular
Lysophospholipids
Wound healing
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....58bd4deee1df55f4b2ce02fdbdb51304